Multiphoton Microscopes Go Big: Large-Scale In Vivo Imaging of Neural Dynamics.

Since the days of Santiago Ramon y Cajal, and pioneering observations of the precise structure of single neurons as the building blocks of the brain, the field of neuroscience has been tasked with deciphering how these individual neuronal elements engender the complexity that defines brain function. This remains a major challenge in modern neuroscience to explain fundamental processes of perception, cognition, and behavior in terms of neural activity. Given the size of the brain, the number of neurons, and the distributed nature of neural activity across interconnected networks, it is increasingly clear that we need advanced systems to directly record this activity in real-time to assess both coordinated activity on a large scale and the brain’s high degree of specialization on a small scale. While seminal principles of brain structure and function have been described through histological examination and in vitro preparations, it is also becoming increasingly evident that a wholistic approach examining the living brain in action is indispensable. These factors combined, the need for multiscale approaches and in situ evaluation of neuronal activity, have fostered rapidly growing technological advances in the field of in vivo microscopy (for review see Kim and Schnitzer, 2022).